Effective treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) requires sufficiently high antibiotic concentrations…

Polymeric microneedle patches represent a promising noninvasive platform for the transdermal delivery of peptide and protein therapeutics, and FDA-approved polymers are widely used for this purpose. H...

Death receptor 5 (DR5) is a key mediator of the extrinsic apoptotic pathway that is often upregulated in tumors, rendering it an attractive target for cancer therapy. Activation of DR5 requires oligom...

Current SARS-CoV-2 vaccines generate short-lived, strain-specific immunity. A polymeric TLR7 agonist nanoparticle (TLR7-NP) adjuvant enhances lymph node targeting and promotes early and sustained ger...

Pulmonary thromboembolism, a pathological condition characterized by the occlusion of pulmonary vasculature by free-circulating thrombus, constitutes the third leading cause of cardiovascular-relat...

Intravenously delivered nanoparticle (NP) therapies have the potential to cure a variety of diseases; however, their clinical use has been stunted by undesirable levels of immune cell clearance. This clearance is attributed to protein adsorption onto the outside of the NPs, leading to recognition by immune cells and subsequent accumulation in the liver and spleen. Membrane-wrapped nanoparticles (MWNPs) offer a potential solution to reducing immune clearance by incorporating immune evasion/marker-of-self-proteins, although they too exhibit protein corona-mediated clearance. While various opsonin proteins can bind to MWNPs, complement proteins are particularly problematic as they play a crucial role in innate immunity, triggering immune cell recognition and clearance and causing inflammation. We hypothesized that introducing a complement regulatory protein into the membranes of MWNPs could minimize complement-mediated clearance, but the opposite effect was observed experimentally. In this study, before membrane collection, source cells were genetically modified to express the complement regulatory protein, CD55, which inhibits C3 convertases, key enzymes in the complement cascade. We confirmed that the active protein was transferred onto MWNPs and determined that CD55-modified MWNPs incubated in mouse serum significantly reduced C3 convertase concentration by 33% compared to unmodified MWNPs. Unexpectedly, in vivo analysis of biodistribution and immune cell uptake showed that CD55-modified MWNPs exhibited 2.1× higher spleen accumulation and elevated immune cell uptake in blood and spleen, specifically in monocyte/macrophage populations, as compared to unmodified MWNPs. This may be due to nonprotein corona-mediated mechanisms, such as the secondary role of CD55 as a ligand for CD97 (expressed in monocytes, macrophages, and other immune cells). Supporting this theory, studies examining ex vivo MWNP binding to spleen cells pretreated with IgG or CD97 antibodies showed that CD55-modified MWNPs had 18% lower binding after CD97 blockade, whereas unmodified MWNP binding was not reduced by CD97 blockade. These findings highlight the importance of considering both serum protein interactions and ligand/receptor interactions when designing genetically engineered MWNPs that overexpress a protein of interest, as well as the importance of testing modified MWNPs in both ex vivo and in vivo settings. In the future, the CD55 modification described here could be utilized to promote spleen tropism of MWNPs when desired. More broadly, this work demonstrates the ability to tune MWNP cellular interactions and biodistribution through genetic engineering of source cells─a technique that can be adapted for a plethora of uses in precision medicine.

Press Release Akina PolySciTech and Corbion Biomaterials Expand Distribution Agreement to Broaden Access to PURASORB® Resorbable Polymer...

This research addresses a significant unmet need in post-operative cardiac care by introducing TIMED, an implantable hydrogel patch with spatially patterned microparticles for programmable, sequential...

The formation of a Protein Corona (PC) on the surface of nanoparticles (NPs) is a critical event that shapes their biological identity and governs interactions with the immune system. In this study, we investigated the composition of the PC formed on mixtures of PLGA and PEG–PLGA NPs, aiming to elucidate the link between NPsurface chemistry, proteomic fingerprint in cell culture medium, and uptake by bone marrow-derived macrophages (BMDMs). NPs showed different sizes but comparable actual PEG amount exposed on the surface, which is significantly lower than the theoretical values. The PC, isolated using a standardized microfiltration protocol, revealed distinct patterns of protein adsorption as a function of the PEG density. Uptake studies in BMDMs revealed a strong inverse relationship between PEG surface density, PC composition, and macrophage internalization, supporting the hypothesis that the opsonin/dysopsonin balance is more critical than a single protein interaction. In conclusion, this work demonstrates that the PEG surface density is not the only determinant of PC composition. These findings underscore the importance of rigorous surface characterization and PC profiling to predict and tune nanocarrier performance in vivo.

The oral route is the most patient-friendly option for drug administration, yet biological barriers often limit its effectiveness. Chief among these i…

Cytokines are potent endogenous modulators of innate immunity, making them key mediators of macrophage plasticity for immunotherapy. However, the clin…

Purpose The present study aimed to determine the relationship between the concentration of myofibroblasts on bovine lens capsules and loss of visual acuity due to monolayer coverage and wrinkling, in a model of an accelerated timeline of posterior capsular opacification (PCO). Methods Bovine lens capsule explants were cultured on 12-well plates and treated with five different concentrations of myofibroblasts, while optical clarity was measured using UV-spectroscopy for a period of 4 days. Immunolocalization studies were carried out to confirm loss of transparency from wrinkling caused by myofibroblastic contractile forces. Novel, injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer hydrogels were engineered for the sustained release of targeted, nucleic acid nanocarriers loaded with cytotoxic doxorubicin (G8:3DNA:Dox). Targeted depletion of myofibroblast precursors using these hydrogels was evaluated. Results Both 25 k and 40 k myofibroblasts/well delivered onto the lens capsule exhibited almost total loss of optical clarity, whereas 5 k and 10 k myofibroblasts/well still showed a significant decrease in transparency. Capsules that received 2 k myofibroblasts/well did not experience a significant reduction in transmittance. Conclusion For the first time, the relationship between myofibroblast concentration, as a result of prolonged exposure to active transforming growth factor-β2 (TGF-β2) and pro-inflammatory conditions, and its effect on lens capsule transparency is shown. The findings of this study can be taken into consideration when designing sustained release devices to prevent the onset of post-surgical complications of cataract surgery.

Nose-to-brain delivery has been widely investigated as a potential strategy for glioma therapy. However, the nasal epithelial barrier remains a major …

Purpose Ovarian cancer (OC) is difficult to detect early; therefore, it is highly likely to advance to peritoneal metastasis at the time of diagnosis. Moreover, multi-drug resistance (MDR) results in ...

Although local colorectal cancer (CRC) therapy can be achieved by delivering CRC-targeted nanoparticles directly to the tumor tissues within the color…

Fetal growth restriction (FGR) affects 5% to 10% of all pregnancies in developed countries and is the second most leading cause of perinatal mortality and morbidity. Life-long consequences of FGR rang...

Leukocyte esterase (LE), markedly upregulated in inflamed colonic tissues, offers a unique enzymatic trigger for selective drug activation in ulcerative colitis (UC). To exploit this pathological hall...

Edaravone is one of the treatment options for Amyotrophic Lateral Sclerosis, but its therapeutic efficacy is limited due to the incapacity to cross the blood–brain barrier, as well as its short life s...

This study elucidates the nanoparticle delivery mechanism occurring at the colorectal lumen–tumor interface for highly selective local colorectal cancer (CRC)-targeted delivery without systemic distr...

Objective Cisplatin is a chemotherapeutic agent with the undesirable side effect of ototoxicity. Transtympanic injections of antioxidant formulations may provide local otoprotection. We tested a nov...